Plasma concentration and vasodilating effect after i.v. bolus injection of stereoisomeric organic nitrates were evaluated. Pharmacokinetics of mononitrates were analyzed with a linear 1-compartment model. The distribution volumes were identical but systemic clearances were different among stereoisomers. The concentration data after dinitrate administration could be described based on a 2-compartment model for dinitrate distribution, with elimination only from central compartment via metabolism to mononitrate, and then mononitrate-dependent metabolic clearance was estimated. In the vasodilation by mononitrate administered intravenously, the maximum effect was not observed. The difference from baseline level of mean arterial pressure (ΔMAP) was related to plasma concentration with a log-linear model, and an identical slope and different intercepts among isomeric mononitrates were obtained. The pharmacological effect following dinitrate dosing were analyzed a sigmoidal Emax model assuming additive effect of dinitrate and mononitrate. Although almost the same Hill's constant and maximum effect values were estimated, EC50 values were different among stereoisomers. The clearance and EC50 values of stereoisomers with nitrate group at the exo position were generally higher than those at the endo position. It suggests that stereostructure of organic nitrates controls the vasodilator potency and duration of action.
